CDSCO Panel Flags Small Sample Size, Limited Scope, Asks Zydus to Rework Phase IV Letermovir Study
New Delhi: The Subject Expert Committee (SEC) under the Central Drugs Standard Control Organization (CDSCO) has directed Zydus Lifesciences Ltd to revise and resubmit the Phase IV Clinical Trial protocol for Letermovir Tablets 240 mg and 480 mg after incorporating the committee's specific recommendations regarding sample size, study endpoints, and coverage of all approved indications.
As per the minutes of the SEC (Antimicrobial & Antiviral) meeting held on 16th September 2025, the firm presented the Phase IV Clinical Trial protocol of Letermovir Tablets 240 mg and 480 mg, vide Protocol No. C2B05804, Version 1.0 (dated 28.05.2025), before the committee. The submission was made in line with the condition of the earlier permission granted for the manufacture and marketing of the drug.
The committee noted that the manufacturing and marketing permission for Letermovir Tablets 240 mg and 480 mg was issued for the following two indications:
For prophylaxis of cytomegalovirus (CMV) infection and disease in adult CMV-seropositive recipients [R+] of an allogeneic hematopoietic stem cell transplant (HSCT). For prophylaxis of CMV disease in adult kidney transplant recipients at high risk (Donor CMV seropositive/ Recipient CMV seronegative [D+/R–]).
However, the committee observed that in the protocol presented, the firm had proposed to assess the safety and efficacy of Letermovir Tablets 240 mg and 480 mg for only one indication, i.e. for prophylaxis of CMV infection and disease in adult CMV-seropositive recipients [R+] of an allogeneic HSCT.
Additionally, the committee noted that the proposed sample size of 40 patients was not adequate to generate sufficient clinical evidence.
After detailed deliberation, the committee recommended that the firm should revise the sample size with justification. It was also opined that the primary outcome should be measured using DNA PCR instead of IgG.
Accordingly, the firm has been instructed to submit the revised clinical trial protocol within one month for further review by the committee. The SEC further recommended that the firm should submit a separate Phase IV study protocol for the second approved indication, i.e. prophylaxis of CMV disease in adult kidney transplant recipients at high risk (Donor CMV seropositive/ Recipient CMV seronegative [D+/R–]).
Letermovir is an antiviral medication that inhibits the CMV DNA terminase complex and is used for the prevention of cytomegalovirus infection and disease in immunocompromised patients. Zydus Lifesciences Ltd, headquartered in Ahmedabad, is an Indian pharmaceutical company engaged in the development and marketing of therapeutic formulations across multiple categories.
